There is experimental evidence which suggests that changes in ventilation during both exposure to hypoxia and during acute metabolic alterations in acid-base balance could be mediated by changes in ventral medullary ECF acidity. The objective of this research is to study the possible role of changes in ventral medullary ECF pH in the regulation of ventilation during these conditions. One component of these responses is the possible modifying effect of concurrent changes in local cerebral blood flow which could act as a brake on the ventilatory response by decreasing the acidity via increased CO2 washout. Studies planned for the coming year: 1) Medullary ECF pH, cisternal CSF pH and ventilatory drive will be measured in spontaneously breathing intact and peripheral chemodenervated cats and rabbits during exposure to hypoxia to determine whether the changes in ventilation can be accounted for by changes in medullary ECF pH; 2) Ventral medullary and total brain flow and ventral medullary ECF pH will be measured during isocapnic and hypocapnic-hypoxia to determine the possible inhibitory effect of the changes in blood flow on ventilatory drive in these conditions; 3) Ventral medullary ECF pH and ventilatory drive will be measured in acute metabolic acidosis and alkalosis to obtain further evidence that the changes in ventilation that occur during metabolic acid-base abnormalities are mediated by changes in ventral medullary ECF pH.